[Basic and clinical study of platelet-derived growth factor gene expression].

PDGF is a glycoprotein composed of A and B chains, and induced the expression not only in platelets but also in many types of cells. By stimulation inducing cell proliferation, transcription of the A chain is activated, resulting in an increase in mRNA. By stimulation inducing cell differentiation, the A chain is activated at the post-transcriptional level, and the B chain at the transcriptional level, resulting in an increase in both mRNA. The 5' region of the A chain shows a mosaic pattern of positive and negative regulatory elements, suggesting complicated regulation. Also the fragments of the first intron are bond by 110Kd and 90Kd nuclear proteins and regulate the A chain expression. Mechanisms of regulation of the A and B chain gene expression differ markedly. The role of PDGF was then investigated on the mechanism of myelofibrosis frequently observed in myeloproliferative disorders (MPD). In the chronic phase of MPD PDGF was suggested to be leaked or released from megakaryocytes. In the accelerated and blast phase of CML with fibrosis, PDGF-AB or PDGF-BB was found to be secreated from myeloid blasts. These results suggest the importance of PDGF in the pathogenesis of myelofibrosis associated with MPD.